Regulated laminin-332 expression in human islets of Langerhans
Regulated laminin-332 expression in human islets of Langerhans
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DOI：
10.1096/fj.08-127142
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发表时间：
2009-12-01
期刊：
影响因子：
4.8
通讯作者：
Bosco, Domenico
中科院分区：
文献类型：
--
作者：
Armanet, Mathieu;Wojtusciszyn, Anne;Bosco, Domenico
层粘连蛋白-332（LN-332）是已知在体外对大鼠胰腺β细胞发挥有益作用的基底膜组分。在这项工作中，我们分析了LN-332在人类胰岛中的表达，其表达后炎症损伤的细胞因子，以及负责这种效果的分子机制。经Western blotting和RT-PCR检测，LN-332在人胰岛中有表达。通过对胰腺切片的免疫荧光，我们观察到标记仅限于胰岛中的内分泌细胞。对分离的胰岛细胞的共聚焦显微镜分析显示，标记是颗粒状的，但不与激素分泌颗粒共定位。与新鲜分离的胰岛相比，LN-332在培养的胰岛中最丰富，并且在培养基中发现，这表明其由胰岛分泌。当胰岛暴露于白细胞介素（IL）-1 β时，LN-332的表达和分泌与对照相比增加。未观察到肿瘤坏死因子（TNF）-α和干扰素（IFN）-γ的影响。磷脂酰肌醇3-激酶（PI 3-K）活性抑制剂LY 294002可抑制培养和IL-1 β诱导的胰岛LN-332表达。这些结果表明，已知在体外对β细胞具有一些有益作用的LN-332由内分泌胰岛细胞产生和分泌，并且通过应激条件如培养和IL-1 β暴露而上调。Armanet，M.，Wojtusciszyn，A.，莫雷尔，P.，Parnaud，G.，P.，Sinigaglia，C.，伯尼，T.，Bosco，D.调节层粘连蛋白-332在人胰岛中的表达FASEB J.23，4046-4055（2009）. www.fasebj.org
Laminin-332 (LN-332) is a basement membrane component known to exert a beneficial effect on rat pancreatic beta cells in vitro. In this work, we analyzed the expression of LN-332 in human islets, its expression after inflammatory insults by cytokines, and the molecular mechanisms responsible for this effect. By Western blotting and RT-PCR, we showed that LN-332 was expressed in isolated human islets. By immunofluorescence on pancreas sections, we observed that labeling was confined to endocrine cells in islets. Confocal microscopy analysis on isolated islet cells revealed that labeling was granular but did not colocalize with hormone secretory granules. LN-332 was most abundant in cultured islets compared to freshly isolated islets and was found in culture medium, which suggests that it was secreted by islets. When islets were exposed to interleukin (IL)-1 beta, expression and secretion of LN-332 increased as compared to control. No effect was observed with tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma. LY294002, an inhibitor of phosphatidylinositol 3-kinase (PI3-K) activity, inhibited culture- and IL-1 beta-induced LN-332 expression in islets. These results show that LN-332, known to have some beneficial effect on beta cells in vitro, is produced and secreted by endocrine islet cells and is up-regulated by stressing conditions such as culture and IL-1 beta-exposure.-Armanet, M., Wojtusciszyn, A., Morel, P., Parnaud, G., Rousselle, P., Sinigaglia, C., Berney, T., Bosco, D. Regulated laminin-332 expression in human islets of Langerhans. FASEB J. 23, 4046-4055 (2009). www.fasebj.org